Search

Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40-60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities.

Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, is projected to see a significant rise in incidence over the next three decades. The precise treatment of PD remains a formidable challenge, prompting ongoing research into early diagnostic methodologies. Network pharmacology, a burgeoning field grounded in systems biology, examines the intricate networks of biological systems to identify critical signal nodes, facilitating the development of multi-target therapeutic molecules. This approach systematically maps the components of Parkinson's disease, thereby reducing its complexity. In this review, we explore the application of network pharmacology workflows in PD, discuss the techniques employed in this field, and evaluate the current advancements and status of network pharmacology in the context of Parkinson's disease. The comprehensive insights will pave newer paths to explore early disease biomarkers and to develop diagnosis with a holistic in silico, in vitro, in vivo and clinical studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Efficient extraction of camptothecin (CPT), an anticancer agent from the commercial source Nothapodytes nimmoniana (J. Graham) Mabb in India, is of paramount importance. CPT is present in the highest concentration in the stem portion, and the stem can be readily harvested without uprooting the plant. The fluorescence microscopy mapping of the bark matrix for CPT revealed its presence in a free form within both the outer (epidermal and cortical tissues) and inner (xylem and phloem tissues) sections. The bark matrix primarily consists of cellulose, hemicellulose, and lignin, rendering it woody, rigid, and resistant to efficient solvent penetration for CPT extraction. We proposed a hypothesis that subjecting it to disruption through treatment with hydrolytic enzymes like cellulase and xylanase could enhance solvent diffusion, thereby enabling a swift and effective extraction of CPT., Objective: The present study was aimed at enzyme-assisted extraction, using cellulase and xylanase for hydrolytic disruption of the cells to readily access CPT from the stem of the plant N. nimmoniana (J. Graham) Mabb., Methodology: The hydrolytic cell disruption of ground powder from the stem bark was studied using cellulase and xylanase enzymes. The enzymatically pretreated stem bark powder was subsequently recovered by filtration, dried, and subjected to extraction with methanol to isolate CPT. This process was optimised through a Box-Behnken design, employing a one-factor-at-a-time approach to assess parameters such as enzyme concentration (2-10% w/w), pH (3-7), incubation time (6-24 h), and solid-to-solvent ratio (1:30-1:70 g/mL). CPT was characterised using proton nuclear magnetic resonance ( 1 H-NMR) and Fourier transform infrared (FTIR) spectra, and a high-performance liquid chromatography (HPLC) method was developed for quantification., Results: The cellulase and xylanase treatment resulted in the highest yields of 0.285% w/w and 0.343% w/w, with efficiencies of 67% and 81%, respectively, achieved in a significantly shorter time compared to the untreated material, which yielded 0.18% with an efficiency of only 42%. Extraction by utilising the predicted optimised process parameters, a nearly two-fold increase in the yield, was observed for xylanase, with incubation and solvent extraction times set at 16 and 2 h, respectively. Scanning electron microscopy (SEM) images of the spent material indicated perforations attributed to enzymatic action, suggesting that this could be a primary factor contributing to the enhanced extraction., Conclusion: Enzyme-mediated hydrolytic cell disruption could be a potential approach for efficient and rapid isolation of CPT from the bark of N. nimmoniana., (© 2024 John Wiley & Sons Ltd.)

Recent research in drug discovery dealing with many faces difficulties, including development of new drugs during disease outbreak and drug resistance due to rapidly accumulating mutations. Virtual screening is the most widely used method in computer aided drug discovery. It has a prominent ability in screening drug targets from large molecular databases. Recently, a number of web servers have developed for quickly screening publicly accessible chemical databases. In a nutshell, deep learning algorithms and artificial neural networks have modernised the field. Several drug discovery processes have used machine learning and deep learning algorithms, including peptide synthesis, structure-based virtual screening, ligand-based virtual screening, toxicity prediction, drug monitoring and release, pharmacophore modelling, quantitative structure-activity relationship, drug repositioning, polypharmacology, and physiochemical activity. Although there are presently a wide variety of data-driven AI/ML tools available, the majority of these tools have, up to this point, been developed in the context of non-communicable diseases like cancer, and a number of obstacles have prevented the translation of these tools to the discovery of treatments against infectious diseases. In this review various aspects of AI and ML in virtual screening of large databases were discussed. Here, with an emphasis on antivirals as well as other disease, offers a perspective on the advantages, drawbacks, and hazards of AI/ML techniques in the search for innovative treatments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Omentectomy is an essential part of cytoreductive surgery (CRS). However, removal of perigastric arcade (PGA) of the omentum is a controversial aspect of omentectomy in view of the fear of injury, vascular compromise and gastroparesis. Hence, we conducted a study to evaluate the necessity and effect of removal of PGA during omentectomy., Methods: The nature of the study was a prospective observational study. The study period was for 1 year between 1.3.2019 and 29.2.2020. Patients with stage III to IV serous epithelial ovarian cancers - chemo naive/post neoadjuvant chemotherapy, without macroscopic involvement of the PGA were included in the study. Patients were divided into two groups - those who had PGA removed (group 1) and those whose PGA was preserved (group 2). Pre, intra and postoperative factors between the two groups were compared using standard statistical methods., Results: Micrometastasis to PGA was present in 36.4% of the patients in group 1. The predictors for this involvement included gross involvement and microscopic involvement of the mobile part of the omentum ( p < 0.001), pre surgery Meyer's score ( p < 0.05) and requirement of peritonectomy ( p < 0.05) during the CRS implying that higher the peritoneal carcinomatosis, more are the chances of microscopic involvement of PGA. On comparing postoperative outcomes between the two groups, we noted a statistically significant difference in intra-operative time ( p < 0.01), prolonged recovery time with increased intensive care unit and hospital stay ( p < 0.001) in group 1, although all with small absolute difference. However, there was no significant difference in major post-operative complications or time taken to tolerate soft diet., Conclusion: Micrometastasis to PGA was noted in significant number of cases. Its removal is also a safe procedure with minimal morbidity and good postoperative outcomes especially in cases with significant peritoneal carcinomatosis. Hence, it should be considered, provided we are achieving a complete cytoreduction otherwise., Competing Interests: There are no conflicts of interest or disclosures., (© the authors; licensee ecancermedicalscience.)

Bhagyalaxmi Nayak Background and Aims  The main objective of this study was to analyze the clinicopathological profile and prognostic factors of granulosa cell tumor (GCT). Method  All the cases of ovarian cancer which were seen at our institute between January 2000 and December 2017 were reviewed. Data were analyzed with failure-free survival (FFS) as the primary end point. Results  GCTs consisted of 2.66% of all ovarian cancers at our institute. The median age was 43 years. Majority of the patients (62.5%) were unstaged. Six patients (25%) had a fertility-preserving procedure. Forty two percent of the patients received adjuvant chemotherapy. Thirty eight percent of the patients developed recurrence. Considering tumor-related prognostic factors, there was a statistically significant decrease in FFS with the presence of hemorrhage ( p  = < 0.001), larger tumors ( p  = 0.042), and juvenile variant ( p  = 0.002). On the contrary, when treatment-related factors were considered, there was no statistically significant improvement in FFS with the performance of lymphadenectomy ( p  = 0.218), omentectomy ( p  = 0.453), fertility sparing surgery ( p  = 0.152), or administration of adjuvant chemotherapy ( p  = 0.45). Conclusion  Inherent tumor-related biological factors tend to play a more important role compared with treatment-related factors in GCTs. Hence, the traditional practice of performance of extensive staging procedures and routine adjuvant chemotherapy should be reviewed. Fertility-preserving surgery appears safe to be offered in early stages when desired. Although it is common knowledge that GCTs tend to be hemorrhagic tumors, this factor has not been well recognized as a prognostic indicator till date. Our study sheds some light on this aspect. Since these tumors have a tendency toward late recurrences, a long follow-up is prudent., Competing Interests: Conflict of Interest None., (MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Aim: This study aimed at screening and development of TG2 inhibitors as anti lung cancer agent., Background: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from the transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative diseases, and also cancer., Objective: The proposed study focused on screening potent inhibitors of TG2 by in-silico method and synthesize their derivative as well as analyse its activity by utilizing an in-vitro approach., Materials and Methods: Molecular docking studies have been carried out on the different classes of TG2 inhibitors against the target protein. Nearly thirty TG2 inhibitors were selected from literature and docking was performed against transglutaminase 2. The computational ADME property screening was also carried out to check their pharmacokinetic properties. The compounds which exhibited positive ADME properties with good interaction while possessing the least binding energy were further validated for their anti-lung cancer inhibition property against A549 cell lines using cytotoxicity studies., Results: The results of the present study indicate that the docked complex formed by cystamine showed better binding affinity towards target protein, so this derivative of cystamine was formed using 2,5 dihydrobenzoic acid. Invitro results revealed that both molecules proved to be good cytotoxic agents against A549 lung cancer (875.10, 553.22 μg/ml), respectively. Further, their activity needs to be validated on TG2 expressing lung cancer., Conclusion: Cystamine and its derivative can act as a potential therapeutic target for lung cancer but its activity should be further validated on TG2 expressing lung cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Imaging techniques are used to capture anomalies of the human body. The captured images must be understood for diagnosis, prognosis and treatment planning of the anomalies. Medical image understanding is generally performed by skilled medical professionals. However, the scarce availability of human experts and the fatigue and rough estimate procedures involved with them limit the effectiveness of image understanding performed by skilled medical professionals. Convolutional neural networks (CNNs) are effective tools for image understanding. They have outperformed human experts in many image understanding tasks. This article aims to provide a comprehensive survey of applications of CNNs in medical image understanding. The underlying objective is to motivate medical image understanding researchers to extensively apply CNNs in their research and diagnosis. A brief introduction to CNNs has been presented. A discussion on CNN and its various award-winning frameworks have been presented. The major medical image understanding tasks, namely image classification, segmentation, localization and detection have been introduced. Applications of CNN in medical image understanding of the ailments of brain, breast, lung and other organs have been surveyed critically and comprehensively. A critical discussion on some of the challenges is also presented., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature 2021.)

Background: Acute haemorrhagic leukoencephalitis (AHLE), a rare variant of acute disseminated encephalomyelitis (ADEM), often presents differently from classical ADEM, thereby posing a diagnostic challenge to the clinician., Aim: To report AHLE, its clinic-radiological manifestations, process of diagnosis and prognosis., Method and Results: Eight patients presented with altered sensorium, acute focal deficits with or without seizures. Initial workup showed evidence of haemorrhagic lobar or thalamic lesions in seven patients. All patients underwent extensive evaluation for collagen vascular disease and vasculitis profile, autoimmune encephalitis panel and aquaporin-4 antibody, which were found to be normal. Cerebrospinal fluid (CSF) biochemistry and microscopy was non-contributory and CSF viral PCRs, toxoplasma antibodies, cryptococcal antigen were also negative. All patients had progressively worsening sensorium and neurological deficits. Repeat MRIs showed increase in oedema in the lesions and appearance/expansion of haemorrhage in the thalamic/hemispherical lesions. All patients received intravenous methylprednisolone (IVMP) without any benefit. Four patients underwent plasmapheresis (PLEX), one received intravenous immunoglobulin (IVIG) and one received both second line immunotherapies, without significant improvement. Brain biopsy (performed in three patients) showed inflammatory demyelination and areas of haemorrhage, thus confirming the diagnosis. Six patients succumbed in 7-30 days of the illness, despite aggressive treatment and only two survived, albeit with a significant disability., Conclusion: AHLE is a rare, yet very severe variant of ADEM. MRI shows lesions with haemorrhages, oedema and mass effect and histology findings reveal inflammatory infiltrates, haemorrhagic foci and fibrinoid necrosis of vessel walls. Prognosis is worse as compared to the classic ADEM, with a high mortality rate. To the best of our knowledge, this is one of the largest series of AHLE to have been reported anywhere in the world., Keymessage: Acute encephalopathy, multifocal deficits accompanied by haemorrhagic CNS demyelinating lesions with oedema and mass effect are the key features of AHLE. It is a rare, yet very severe form of ADEM with very high morbidity and mortality., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Medial coronal plane malalignment, also known as varus alignment, is commonly reported in osteoarthritic knees. Although the degree of deformity provides some insight regarding the severity of the disease, it does not always reflect the potential complexity of the surgical treatment., Methods: This prospective observational study was conducted by analyzing the radiographs of 100 consecutive knees in patients undergoing total knee arthroplasty. For each knee, coronal alignment, expressed as the hip-knee-ankle angle, was measured on a full-leg standing radiograph and classified in 3 stages. The primary location of the varus deformity was identified as intra-articular and/or extra-articular. Additionally, knees were evaluated to assess for 10 radiographic features of varus deformity and then classified in 3 grades of osteoarthritis severity., Results: The mean (and standard deviation) preoperative varus deformity was 11° ± 6° of varus (hip-knee-ankle, 169°), as measured on standardized full-leg radiographs. Extra-articular varus deformity was observed in 14% of patients. A higher number of radiographic features of varus severity corresponded with higher degrees of deformity. Varus grade correlated strongly with stage of varus deformity. Twenty-three (100%) of 23 stage-III deformities had grade-C features; however, 13 (48%) of 27 stage-I patients also had grade-C disease., Conclusions: One of every 7 osteoarthritis patients with varus deformity had an extra-articular deformity, and 1 of 2 of these patients had severe intra-articular disease (grade C) despite limited coronal deformity (stage I). These findings reconfirm the need for individual deformity analysis that accounts for the degree, location, and severity of the varus deformity. This insight may help to formulate an algorithmic treatment approach specific to the epiphyseal knee anatomy of the patient and according to the surgical preferences of the surgeon., Clinical Relevance: Knee surgeons tend to consider knees with higher degrees of coronal deformity as more technically difficult, but the present study shows that knees with less deformity can still present with severe grades of osteoarthritis inside the knee, leading to more challenging joint reconstruction., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/A769)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Neurosyphilis (NS) is a rarely encountered scenario today. Manifestations are heterogeneous, and their characteristics have changed in the antibiotic era. A differential diagnosis of NS is not commonly thought of even with relevant clinical-radiological features, as it mimics many common neurological syndromes., Objectives: To study the manifestations of NS in the present era and the process of diagnosis., Method: The data of ten patients with NS was collected and analyzed. Their background data, clinical features, investigations, the process of reaching the diagnosis, management and outcomes were recorded., Observations and Results: The manifestations of NS in our cohort included six patients with cognitive decline/encephalopathy and one each with meningitis with cranial nerve palsies, cerebellar ataxia, myelitis and asymptomatic NS. The presence of Argyll Robertson pupil helped to clinch diagnosis in one patient. Treponemal tests were ordered in two patients only after alternative etiologies were looked at, to begin with, whereas in six patients treponemal test was requested as a part of standard workup for dementia/ataxia., Conclusions: NS dementia and behavior changes are mistaken for degenerative, vascular, nutritional causes, autoimmune encephalitis or prion disease. Meningitis has similarities with infective (tubercular), granulomatous (sarcoidosis, Wegener's), collagen vascular disease and neoplastic meningitis, and myelitis simulates demyelination or nutritional myelopathy (B 12 deficiency). Rarely, NS can also present with cerebellar ataxia. Contemplate NS as one of the rare causes for such syndromes, and its early treatment produces good outcomes., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2021 Annals of Indian Academy of Neurology.)

Background: Discovery of serum myelin oligodendrocyte glycoprotein (MOG) antibody testing in demyelination segregated MOG-IgG disease from AQ-4-IgG positive NMOSD., Aims: To study clinico-radiological manifestations, pattern of laboratory and electrophysiological investigations and response to treatment through follow up in MOG-IgG positive patients., Method: Retrospective data of MOG-IgG positive patients was collected. Demographics, clinical manifestations at onset and at follow up and relapses, anti AQ-4-IgG status, imaging and all investigations were performed, treatment of relapses and further immunomodulatory therapy were captured., Results: In our 30 patients, F: M ratio was 2.75:1 and adult: child ratio 4:1. Relapses at presentation were optic neuritis {ON}(60%), longitudinally extensive transverse myelitis {LETM}(20%), acute disseminated encephalomyelitis {ADEM}(13.4%), simultaneous ON with myelitis (3.3%) and diencephalic Syndrome (3.3%). Salient MRI features were ADEM-like lesions, middle cerebellar peduncle fluffy infiltrates, thalamic and pontine lesions and longitudinally extensive ON {LEON} as well as non-LEON. Totally, 50% patients had a relapsing course. Plasma exchange and intravenous immunoglobulin worked in patients who showed a poor response to intravenous methylprednisolone. Prednisolone, Azathioprine, Mycophenolate and Rituximab were effective attack preventing agents., Conclusions: MOG-IgG related manifestations in our cohort were monophasic/recurrent/simultaneous ON, myelitis, recurrent ADEM, brainstem encephalitis and diencephalic Syndrome. MRI features suggestive of MOG-IgG disease were confluent ADEM-like lesions, middle cerebellar peduncle fluffy lesions, LETM, LEON and non-LEON. Where indicated, patients need to go on immunomodulation as it has a relapsing course and can accumulate significant disability. Because of its unique manifestations, it needs to be considered as a distinct entity. To the best of our knowledge, this is the largest series of MOG-IgG disease reported from India., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2021 Annals of Indian Academy of Neurology.)

The application of lipid-based drug delivery technologies for bioavailability enhancement of drugs has led to many successful products in the market for clinical use. Recent studies on amine-containing heterolipid-based synthetic vectors for delivery of siRNA have witnessed the United States Food and Drug Administration (USFDA) approval of the first siRNA drug in the year 2018. The studies on various synthetic lipids investigated for delivery of such nucleic acid therapeutics have revealed that the surface p K a of the constructed nanoparticles plays an important role. The nanoparticles showing p K a values within the range of 6-7 have performed very well. The development of high-performing lipid vectors with structural diversity and falling within the desired surface p K a is by no means trivial and requires tedious trial and error efforts; therefore, a practical solution is called for. Herein, an attempt to is made provide a solution by predicting the statistically significant p K a through a predictive quantitative structure-activity relationship (QSAR) model. The QSAR model has been constructed using a series of 56 amine-containing heterolipids having measured p K a values as a data set and employing a partial least-squares regression coupled with stepwise (SW-PLSR) forward algorithm technique. The model was tested using statistical parameters such as r 2 , q 2 , and pred&#95; r 2 , and the model equation explains 97.2% ( r 2 = 0.972) of the total variance in the training set and it has an internal ( q 2 ) and an external (pred&#95; r 2 ) predictive ability of ∼83 and ∼63%, respectively. The model was validated by synthesizing a series of designed heterolipids and comparing measured surface p K a values of their nanoparticle assembly using a 2-( p -toluidino)-6-napthalenesulfonic acid (TNS) assay. Predicted and measured surface p K a values of the synthesized heterolipids were in good agreement with a correlation coefficient of 93.3%, demonstrating the effectiveness of this QSAR model. Therefore, we foresee that our developed model would be useful as a tool to cut short tedious trial and error processes in designing new amine-containing heterolipid vectors for delivery of nucleic acid therapeutics, especially siRNA., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Purpose: Pancreatic malignancy with mesenterico-portal venous involvement can be safely managed with en bloc vein resection with comparable survival outcomes. Non-constructible venous encasement is regarded as criteria of unresectability in pancreatic cancer. In long-standing extra-hepatic venous obstruction, hepatopetal blood flow is established by collateralization in the hepatoduodenal and mesenteric region. Their importance in pancreatic malignancies is being recently acknowledged., Methods: The records of patients undergoing pancreatoduodenectomies were retrospectively evaluated from 2012 to 2019. Pre and intraoperative records of patients undergoing concomitant vein resection were evaluated for the presence of venous collaterals, and its impact on oncological management was studied., Results: Over a period of 7 years, 947 pancreatoduodenectomies were performed, of which 56 patients underwent concomitant vein resection. Among these, six patients had significant collaterals due to venous obstruction. They had pancreatic adenocarcinoma (2), neuroendocrine tumour (2) and solid pseudopapillary epithelial neoplasm (2) respectively. All these patients successfully underwent pancreatoduodenectomy with vein resection without vascular reconstruction. Superior mesenteric vein (SMV) was resected in four patients, whereas spleno-portal junction was resected in two patients. Dominant collaterals were preserved in all, without compromising oncological safety. Bowel congestion was checked by tolerability to 20-minute mesenteric venous clamping test. There was no major morbidity or hospital mortality following this surgical approach., Conclusion: We recommend vein resection without reconstruction (VROR) as a novel approach in locally advanced pancreatic tumours (due to non-constructible vein involvement) with significant venous collaterals and emphasize the need to assess venous collateralization pre and intraoperatively.

Background: Adductor canal block (ACB) is one of the preferred methods of analgesia in total knee arthroplasty (TKA). However, conventionally its use is time-consuming, requires ultrasound guidance, a trained anaesthesia team and adherence to strict asepsis by members of the allied teams. This study was done to assess the feasibility and safety of direct adductor canal block (DACB) as a part of surgeon-administered periarticular infiltration., Materials and Methods: Thirty computed tomography (CT) angiography films of the patients were retrospectively reviewed. The trajectory of the needle placement for a DACB in relation to the target region of the adductor block was determined. Fourteen knees in seven cadavers, were dissected through a medial parapatellar approach to perform TKA. After administering the DACB using the technique based on CT data, dissection was carried out to ascertain the correct placement of the dye by visualising the stained areas., Results: The angle of approach in the coronal plane from the entry point to the medial high point and to the adductor hiatus was 10.2° (8-14°) and 6° (3.8-11°), respectively. The angle of approach in the sagittal plane from the entry point to the medial high point and to the adductor hiatus was 7° (5-10.5°) and 29° (19-43°), respectively. In all the 14 cadaveric knees, we confirmed the correct placement of the methylene blue dye as demonstrated by the staining of the adductor canal., Conclusion: The study demonstrates the feasibility of the DACB. This surgeon-driven technique is likely to reduce the cost of the procedure, reduce operating room time and also eliminate the risks of surgical-site contamination.

Objective: Patients exposed to chronic sustained hypoxia frequently develop cardiovascular disease risk factors to ultimately succumb to adverse cardiovascular events. In this context, the present study intends to assess the role of cilnidipine (Cil), a unique calcium channel blocker that blocks both L-type and N-type calcium channels, on cardiovascular pathophysiology in face of chronic sustained hypoxia exposure., Materials and Methods: The study involved Wistar strain albino rats. The group-wise allocation of the experimental animals is as follows - Group 1, control (21% O 2 ); Group 2, chronic hypoxia (CH) (10% O 2 , 90% N); Group 3, Cil + 21% O 2 ; and Group 4, CH (10% O 2 , 90% N) + Cil (CH + Cil). Cardiovascular hemodynamics, heart rate variability, and endothelial functions (serum nitric oxide [NO], serum endothelial nitric oxide synthase [NOS3], and serum vascular endothelial growth factor [VEGF]) were assessed. Cardiovascular remodeling was studied by histopathological examination of the ventricular tissues, coronary artery (intramyocardial), and elastic and muscular arteries. Normalized wall index of the coronary artery was also calculated., Results and Conclusion: The results demonstrated altered cardiovascular hemodynamics, disturbed cardiovascular autonomic balance, increased levels of VEGF and NOS3, and decreased bioavailability of NO on exposure to chronic sustained hypoxia. The histopathological examination further pointed toward cardiovascular remodeling. Treatment with Cil ameliorated the cardiovascular remodeling and endothelial dysfunction induced by CH exposure, which may be due to its blocking actions on L/N-type of calcium channels, indicating the possible therapeutic role of Cil against CH-induced cardiovascular pathophysiology., Competing Interests: None

Nickel, a widely used heavy metal is suspected as a cardiotoxic element. The aim of the present study was to assess the possible protective role of l-ascorbic acid on nickel-induced alterations of cardiovascular pathophysiology in male albino rats. Twenty-four albino rats (b.wt. 170-250 g) were randomized into four groups: control; l-ascorbic acid (50 mg/100 g b.wt., orally); NiSO 4 (2.0 mg/100 g b.wt., i.p.); NiSO 4 with l-ascorbic acid. Cardiovascular electrophysiology, serum and cardiac tissue malondialdehyde (MDA), nitric oxide (NO), ascorbic acid, serum α-tocopherol and serum vascular endothelial growth factor (VEGF) were evaluated. Histopathology of cardiac and aortic tissues was also assessed. NiSO 4 -treated rats showed a significant increase in heart rate, LF/HF ratio and blood pressure (SBP, DBP and MAP). A significant increase of serum MDA, NO and VEGF in NiSO 4 treatment with a concomitant decrease of serum ascorbic acid and α-tocopherol as compared to their respective controls were also observed. Simultaneous supplementation of l-ascorbic acid with NiSO 4 significantly decreased LF/HF ratio, BP and oxidative stress parameters, whereas ascorbic acid and α-tocopherol concentration was found to be increased. Histopathology of cardiac and aortic tissues showed nickel-induced focal myocardial hypertrophy and degeneration in cardiac tissue with focal aneurism in aortic tissues. Supplementation with l-ascorbic showed a protective action in both cardiac and aortic tissues. Results indicated the possible beneficial effect of l-ascorbic acid on nickel-induced alteration of the cardiovascular pathophysiology in experimental rats.

Gene expression is an inherently stochastic process with transcription of mRNAs often occurring in bursts: short periods of activity followed by typically longer periods of inactivity. While a simple model involving switching between two promoter states has been widely used to analyze transcription dynamics, recent experimental observations have provided evidence for more complex kinetic schemes underlying bursting. Specifically, experiments provide evidence for complexity in promoter dynamics during the switch from the transcriptionally inactive to the transcriptionally active state. An open question in the field is: what is the minimal complexity needed to model promoter dynamics and how can we determine this? Here, we show that measurements of mRNA fluctuations can be used to set fundamental bounds on the complexity of promoter dynamics. We study models wherein the switching time distribution from transcriptionally inactive to active states is described by a general waiting-time distribution. Using approaches from renewal theory and queueing theory, we derive analytical expressions which connect the Fano factor of mRNA distributions to the waiting-time distribution for promoter switching between inactive and active states. The results derived lead to bounds on the minimal number of promoter states and thus allow us to derive bounds on the minimal complexity of promoter dynamics based on single-cell measurements of mRNA levels.

In this report, novel pH-sensitive interpenetrated network (IPN) polyspheres were developed utilizing polyacrylamide-g-locust bean gum (PAAm-g-LBG) in combination with sodium alginate (SA) to achieve intestinal targeted delivery of ketoprofen. PAAm-g-LBG was synthesized under microwave irradiation wherein ceric ammonium nitrate was used as reaction initiator and then conversion of PAAm-g-LBG as pH-sensitive copolymer was carried out by alkaline hydrolysis. The PAAm-g-LBG copolymer was characterized through 1 H-NMR, FTIR and elemental analysis. The IPN polyspheres exhibited pH-depended swelling or de-swelling with the alteration of surrounding pH. The in-vitro release of drug from IPN polyspheres was found to be higher (≈ 90%) in phosphate buffer of pH 7.4 in comparison with that in pH 1.2 buffer (10.6%). The in-vivo pharmacokinetic, anti-inflammatory screening and stomach histopathology studies performed on Wistar rats revealed pH sensitivity of IPN polyspheres where ketoprofen was successfully targeted to small intestine resulting in reduced side effects of ketoprofen like ulcer formation, erosion of gastric mucosa and hemorrhages., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Phenotypic heterogeneity in cancer cells is widely observed and is often linked to drug resistance. In several cases, such heterogeneity in drug sensitivity of tumors is driven by stochastic and reversible acquisition of a drug tolerant phenotype by individual cells even in an isogenic population. Accumulating evidence further suggests that cell-fate transitions such as the epithelial to mesenchymal transition (EMT) are associated with drug resistance. In this study, we analyze stochastic models of phenotypic switching to provide a framework for analyzing cell-fate transitions such as EMT as a source of phenotypic variability in drug sensitivity. Motivated by our cell-culture based experimental observations connecting phenotypic switching in EMT and drug resistance, we analyze a coarse-grained model of phenotypic switching between two states in the presence of cytotoxic stress from chemotherapy. We derive analytical results for time-dependent probability distributions that provide insights into the rates of phenotypic switching and characterize initial phenotypic heterogeneity of cancer cells. The results obtained can also shed light on fundamental questions relating to adaptation and selection scenarios in tumor response to cytotoxic therapy.

Alcohols are the essential chemicals used in a variety of pharmaceutical and chemical industries. The extreme purity of alcohols in many of such industrial applications is essential. Though distillation is one of the methods used conventionally to purify alcohols, the method consumes more energy and requires carcinogenic entertainers, making the process environmentally toxic. Alternatively, efforts have been made to focus research efforts on alcohol dehydration by the pervaporation (PV) separation technique using polymeric membranes. The present review is focused on alcohol dehydration using PV separation technique, which is the most efficient and benign method of purifying alcohols that are required in fine chemicals synthesis and developing pharmaceutical formulations. This review will discuss about the latest developments in the area of PV technique used in alcohol dehydration using a variety of novel membranes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We present a reformulation of the distance metric learning problem as a penalized optimization problem, with a penalty term corresponding to the von Neumann entropy of the distance metric. This formulation leads to a mapping to statistical mechanics such that the metric learning optimization problem becomes equivalent to free energy minimization. Correspondingly, our approach leads to an analytical solution of the optimization problem based on the Boltzmann distribution. The mapping established in this work suggests new approaches for dimensionality reduction and provides insights into determination of optimal parameters for the penalty term. Furthermore, we demonstrate that the metric projects the data onto direction of maximum dissimilarity with optimal and tunable separation between classes and thus the transformation can be used for high dimensional data visualization, classification, and clustering tasks. We benchmark our method against previous distance learning methods and provide an efficient implementation in an R package available to download at: https://github.com/kouroshz/fenn.

Aim: This questionnaire-based national survey is aimed at understanding the patterns of practice of various aspects of central nervous system (CNS) tuberculosis (TB) among neurologists., Settings and Design: Neurology department of a tertiary medical college., Materials and Methods: A questionnaire was sent through email to all practicing neurologists in India. The responses were analyzed., Statistical Analysis: Inferential statistics., Results: In all, 144 responses were received (out of the 853 questionnaires sent). The major discrepancies were in the primary antitubercular drug regimen (HRZE + HR), duration for tubercular meningitis (TBM) [12 months] and tuberculoma (12-18 months) to develop, follow-up (varied), linezolid use (varied), proportion of drug-resistant cases (<25%), and not taking histological aids (91%). The cerebrospinal fluid (CSF) TB polymerase chain reaction (PCR) utility (75%), not using CSF adenosine deaminase [ADA] (58%), the strategy to stop antitubercular drugs, and the use of steroids (77%) were according to guidelines., Conclusion: The present survey, for the first time, provides ground-level evidence of various aspects of CNS TB as practiced by neurologists in India. The major diversity was observed in therapeutics such as the choice of antitubercular drugs, its duration, linezolid use beyond the recommended duration, and knowledge of drug resistance. The monitoring aspects of CNS TB also showed variations. The investigational aspects of CNS TB such as using TB PCR, not using CSF ADA, and regular neuroimaging revealed a good clinical practice. Other CSF parameters require uniformity. This survey thus helps to identify areas of future work in CNS TB in India., Competing Interests: There are no conflicts of interest

The paper and pulp industry (PPI) produces high quantities of solid and liquid discharge and is regarded as the most polluting industry in the world causing adverse effects to environments and human beings. Hence changes in the way PPI sludge and waste materials are treated is urgently required. Nearly, 10 million tons of waste is generated per year, however PPI waste is enriched with many organic chemicalscontaining a high percentage of lignin, cellulose, and hemicellulose which can be used as valuable raw materials for the production of bioenergy and value-added chemicals. Pretreatment of complex lignocellulosic materials of PPI waste is difficult because of the cellulose crystallinity and lignin barrier. At present most of this waste is recycled in a conventional treatment approach through biological and chemical processes, incurring high cost and low returns. Henceefficient pretreatment techniques are required by which complete conversion of PPI waste is possible. Therefore, the present chapter provides the scope of integration of pretreatment methods through which bioenergy recovery is possible during the PPI waste treatment. Detailed information is presented on the various pre-treatment techniques (chemical, mechanical, enzymatic and biological) in order to increase the efficiency of PPI waste treatment and energy recovery from PPI waste. Along with acid and alkali based efficient chemical treatment process, physical methods (i.e. shearing, high-pressure homogenization, etc.), biochemical techniques (whole cell-based and enzyme-based) and finally biological techniques (e.g. aerobic and anaerobic treatment) are discussed. During each of the treatment processes, scope of energy recovery and bottlenecks of the processes were elaborated. The review thus provides systemic insight into developing efficient pretreatment processes which could increase carbon recovery and treatment efficiency of PPI waste., (Copyright © 2019. Published by Elsevier B.V.)

Post-transcriptional regulation of gene expression is often a critical component of cellular processes involved in cell-fate decisions. Correspondingly, considerable efforts have focused on modeling post-transcriptional regulation of stochastic gene expression and on quantifying its impact on the mean and variance of protein levels. However, the impact of post-transcriptional regulation on rare events corresponding to large deviations in gene expression is less well understood. Here, we study a simple model involving post-transcriptional control of gene expression and characterize the impact of regulation on large deviations in activity fluctuations. We derive analytical results for the large deviation function for protein production rate and for the corresponding driven process which characterizes system fluctuations conditional on the rare event. Our results suggest that fluctuations in burst size rather than frequency play a dominant role in controlling rare events. The results derived also provide insight into how post-transcriptional regulation can be used to fine-tune the probability of rare fluctuations and to thereby control phenotypic variation in a population of cells.

An electro-responsive PAAm-g-Dxt copolymer was synthesized and characterized by 1 HNMR & FTIR spectroscopy, neutralization equivalent, elemental and thermogravimetric analysis to ascertain the grafting reaction. Further, we developed an electro-responsive transdermal drug delivery system (ETDS) utilizing PAAm-g-Dxt copolymer for rivastigmine tartarate delivery through skin. The ETDS were developed using drug-loaded PAAm-g-Dxt hydrogel as the reservoir, and cross-linked dextran-poly(vinyl alcohol) blend films as rate controlling membranes (RCM). In the absence of electrical stimuli, a small amount of drug was permeated from the ETDS, while in the presence of electrical stimuli, the drug permeability was increased. On application of electric stimulus, the flux was increased by 1.6 fold; drug permeability was enhanced when the strength of applied electric current was raised to 8 mA from 2 mA. The drug permeability characteristics studied under "on-off" stimuli suggested that there was faster drug permeation when electrical stimuli was 'on' and it decreased when electrical stimuli was 'off.' The histopathology study confirmed the altered skin structural integrity after application of electrical stimuli. Hence, the PAAm-g-Dxt based ETDS are useful for transdermal drug delivery triggered by an electric stimulus to deliver on-demand release of drug into systemic circulation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Prebiotics plays an important role in improving the growth of gut bacteria and it majorly found in various natural food sources such as fruits and vegetables. Nowadays, the prebiotic sources are added as a supplement in various food products such as dairy products, beverages, health drinks, infant formulae, and meat products. The presence of prebiotics provides various health benefits such as improveing calcium and magnesium absorption, increases bone density, reduces cancer risk, decreases cardiovascular diseases and also improves the immune system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Noncoding small RNAs (sRNAs) are known to play a key role in regulating diverse cellular processes, and their dysregulation is linked to various diseases such as cancer. Such diseases are also marked by phenotypic heterogeneity, which is often driven by the intrinsic stochasticity of gene expression. Correspondingly, there is significant interest in developing quantitative models focusing on the interplay between stochastic gene expression and regulation by sRNAs. We consider the canonical model of regulation of stochastic gene expression by sRNAs, wherein interaction between constitutively expressed sRNAs and mRNAs leads to stoichiometric mutual degradation. The exact solution of this model is analytically intractable given the nonlinear interaction term between sRNAs and mRNAs, and theoretical approaches typically invoke the mean-field approximation. However, mean-field results are inaccurate in the limit of strong interactions and low abundances; thus, alternative theoretical approaches are needed. In this work, we obtain analytical results for the canonical model of regulation of stochastic gene expression by sRNAs in the strong interaction limit. We derive analytical results for the steady-state generating function of the joint distribution of mRNAs and sRNAs in the limit of strong interactions and use the results derived to obtain analytical expressions characterizing the corresponding protein steady-state distribution. The results obtained can serve as building blocks for the analysis of genetic circuits involving sRNAs and provide new insights into the role of sRNAs in regulating stochastic gene expression in the limit of strong interactions., (Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

CsrA/RsmA is a RNA-binding protein that functions as a global regulator controlling important processes such as virulence, secondary metabolism, motility, and biofilm formation in diverse bacterial species. The activity of CsrA/RsmA is regulated by small RNAs that contain multiple binding sites for the protein. The expression of these noncoding RNAs effectively sequesters the protein and reduces free cellular levels of CsrA/RsmA. While multiple bacterial small RNAs that bind to and regulate CsrA/RsmA levels have been discovered, it is anticipated that there are several such small RNAs that remain undiscovered. To assist in the discovery of these small RNAs, we have developed a bioinformatics approach that combines sequence- and structure-based features to predict small RNA regulators of CsrA/RsmA. This approach analyzes structural motifs in the ensemble of low energy secondary structures of known small RNA regulators of CsrA/RsmA and trains a binary classifier on these features. The proposed machine learning approach leads to several testable predictions for small RNA regulators of CsrA/RsmA, thereby complementing and accelerating experimental efforts aimed at discovery of noncoding RNAs in the CsrA/RsmA pathway.

An effort was made to formulate and evaluate pH-sensitive spray dried microspheres using hydrolyzed polyacrylamide-graft-gum karaya (PAAm-g-GK) for colon specific delivery of an anti-cancer agent, capecitabine. The synthesis of pH-sensitive PAAm-g-GK copolymer was done by free radical polymerization followed by alkaline hydrolysis and characterized satisfactorily. The microspheres were spherical in shape; drug entrapment efficiency was found to be in the range of 77.30% to 88.74%. Pulsatile swelling study indicates that the PAAm-g-GK consists of considerable pH-sensitivity. The in-vitro drug release suggested that the microspheres prepared using native GK were incapable to retard the drug release within 5h in the environment of stomach and small intestine. While, those microspheres prepared using pH-sensitive PAAm-g-GK copolymer having crosslinked with glutaraldehyde (GA), released little amount of drug within 5h, but maximum amount of drug was targeted to colonic region in a controlled manner up to 24h. For example, GK10 Microspheres showed only 19.16% drug release at the end of 5th h, while about 80.14% of drug was targeted to colonic region. Cross-linking with GA reduced the early drug release in the upper part of gastrointestinal tract and guaranteed maximum drug release in the colonic region. A rapid enhancement in drug release was witnessed in rat caecal content medium due to the action of colonic bacteria on PAAm-g-GK copolymer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Regulation by microRNAs (miRNAs) and modulation of miRNA activity are critical components of diverse cellular processes. Recent research has shown that miRNA-based regulation of the tumor suppressor gene PTEN can be modulated by the expression of other miRNA targets acting as competing endogenous RNAs (ceRNAs). However, the key sequence-based features enabling a transcript to act as an effective ceRNA are not well understood and a quantitative model associating statistical significance to such features is currently lacking. To identify and assess features characterizing target recognition by PTEN-regulating miRNAs, we analyze multiple datasets from PAR-CLIP experiments in conjunction with RNA-Seq data. We consider a set of miRNAs known to regulate PTEN and identify high-confidence binding sites for these miRNAs on the 3' UTR of protein coding genes. Based on the number and spatial distribution of these binding sites, we calculate a set of probabilistic features that are used to make predictions for novel ceRNAs of PTEN. Using a series of experiments in human prostate cancer cell lines, we validate the highest ranking prediction (TNRC6B) as a ceRNA of PTEN. The approach developed can be applied to map ceRNA networks of critical cellular regulators and to develop novel insights into crosstalk between different pathways involved in cancer.

The intrinsic stochasticity of gene expression can give rise to large fluctuations and rare events that drive phenotypic variation in a population of genetically identical cells. Characterizing the fluctuations that give rise to such rare events motivates the analysis of large deviations in stochastic models of gene expression. Recent developments in non-equilibrium statistical mechanics have led to a framework for analyzing Markovian processes conditioned on rare events and for representing such processes by conditioning-free driven Markovian processes. We use this framework, in combination with approaches based on queueing theory, to analyze a general class of stochastic models of gene expression. Modeling gene expression as a Batch Markovian Arrival Process (BMAP), we derive exact analytical results quantifying large deviations of time-integrated random variables such as promoter activity fluctuations. We find that the conditioning-free driven process can also be represented by a BMAP that has the same form as the original process, but with renormalized parameters. The results obtained can be used to quantify the likelihood of large deviations, to characterize system fluctuations conditional on rare events and to identify combinations of model parameters that can give rise to dynamical phase transitions in system dynamics.

Unique pH-sensitive spray dried microspheres were formulated employing hydrolyzed polyacrylamide-g-carboxymethylcellulose sodium (PAAm-g-NaCMC) co-polymer for colon targeted delivery of an anticancer drug, capecitabine. Synthesis of PAAm-g-NaCMC was carried out through free radical polymerization, which was supported with an inert atmosphere and then the alkaline hydrolysis was performed and subjected for characterization including FTIR spectroscopic analysis, 1 H NMR spectroscopic analysis, elemental analysis, viscosity measurement, neutralization equivalent and thermo-gravimetric investigation. The swelling data suggested that the PAAm-g-NaCMC possesses significant pH-sensitive property. The microspheres were in the range of 1.00 to 7.34 μ and the drug entrapment efficiency ranged between 70.98 and 94.41%. In vitro drug release suggested the failure of microspheres formulated using native NaCMC which failed to impede drug release in stomach and small intestine, while those prepared with pH-sensitive PAAm-g-NaCMC copolymer and cross-linked with glutaraldehyde are suitable for colon targeting because they retarded release of drug in physiologic atmosphere of stomach and small intestine. Only 12.97% of drug was released from CMC10 formulation by the end of 5th h and rest of drug has been targeted to colonic region. A sudden increase in release of drug was observed in rat caecal contents media because of colonic bacterial action on PAAm-g-NaCMC copolymer.

The sporadic nature of gene expression at the single-cell level-long periods of inactivity punctuated by bursts of mRNA or protein production-plays a critical role in diverse cellular processes. To elucidate the cellular role of bursting in gene expression, synthetic biology approaches have been used to design simple genetic circuits with bursty mRNA or protein production. Understanding how such genetic circuits can be designed with the ability to control burst-related parameters requires the development of quantitative stochastic models of gene expression. In this work, we analyze stochastic models for the regulation of gene expression bursts by strongly interacting small RNAs. For the parameter range considered, results based on mean-field approaches are significantly inaccurate and alternative analytical approaches are needed. Using simplifying approximations, we obtain analytical results for the corresponding steady-state distributions that are in agreement with results from stochastic simulations. These results indicate that regulation by small RNAs, in the strong interaction limit, can be used to effectively modulate the frequency of bursting. We explore the consequences of such regulation for simple genetic circuits involving feedback effects and switching between promoter states.

Inflammatory bowel disease (IBD) is an inflammatory condition with mucosal ulceration, edema and hemorrhage of gastrointestinal tract. Curcumin has been shown to mitigate colitis in animal models. However, its usefulness is reduced due to poor pharmacokinetic behavior and low oral bioavailability. To address this, novel pH-sensitive hydrolyzed polyacrylamide-grafted-xanthan gum (PAAm-g-XG) nanoparticles (NPs) loaded with curcumin were prepared for colonic delivery. Optimized nanoparticles (CN20) were spherical, with an average size of 425 nm. A negligible amount of curcumin (≈8%) was released from CN20 NPs in pH 1.2 and 4.5 solutions. When the pH was increased to 7.2, curcumin release was comparatively faster than that observed with pH 1.2 and 4.5 collectively. In pH 6.8 solution, excellent release of curcumin was observed. Highest curcumin release was observed when rat caecal contents were incorporated in pH 6.8 solution, indicating microflora-dependent drug release property of NPs. In acetic acid-induced IBD in rats, curcumin NPs reduced myeloperoxidase and nitrite levels, prevented weight loss and attenuated colonic inflammation. Curcumin was better absorbed systemically in nanoparticulate form with increased Cmax (∼3 fold) and AUC (∼2.5 fold) than when delivered as free curcumin. We demonstrate successful development of grafted co-polymeric NPs containing drug suitable for colon targeting., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Gene expression in individual cells is highly variable and sporadic, often resulting in the synthesis of mRNAs and proteins in bursts. Such bursting has important consequences for cell-fate decisions in diverse processes ranging from HIV-1 viral infections to stem-cell differentiation. It is generally assumed that bursts are geometrically distributed and that they arrive according to a Poisson process. On the other hand, recent single-cell experiments provide evidence for complex burst arrival processes, highlighting the need for analysis of more general stochastic models. To address this issue, we invoke a mapping between general stochastic models of gene expression and systems studied in queueing theory to derive exact analytical expressions for the moments associated with mRNA/protein steady-state distributions. These results are then used to derive noise signatures, i.e. explicit conditions based entirely on experimentally measurable quantities, that determine if the burst distributions deviate from the geometric distribution or if burst arrival deviates from a Poisson process. For non-Poisson arrivals, we develop approaches for accurate estimation of burst parameters. The proposed approaches can lead to new insights into transcriptional bursting based on measurements of steady-state mRNA/protein distributions.

This article reports the development of pH-sensitive interpenetrating polymer network (IPN) microbeads using polyacrylamide-grafted-gum ghatti (PAAm-g-GG) and sodium alginate (SA) for gastro-protective controlled delivery of ketoprofen. We have synthesized PAAm-grafted-GG copolymer under microwave irradiation using cerric ammonium nitrate as reaction initiator; further, the PAAm-g-GG was converted to pH-sensitive copolymer through alkaline hydrolysis. Sophisticated instrumentation techniques were used to characterize PAAm-g-GG. The IPN microbeads of PAAm-g-GG and SA, pre-loaded with ketoprofen were prepared by dual crosslinking using Ca(2+) ions and glutaraldehyde (GA). The IPN microbeads demonstrated excellent pH-sensitive behavior as noted in the pulsatile swelling test and scanning electron microscopy. IPN microbeads also showed larger amount of drug release in buffer solution of pH 7.4 as compared to drug release in solution of pH 1.2. The in vivo pharmacokinetic, pharmacodynamic and stomach histopathology studies conducted on wistar rats confirmed the pH-sensitive controlled release of ketoprofen; IPN microbeads retarded the drug release in stomach resulting in reduced adverse effects of ketoprofen., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Mucormycosis is an opportunistic fungal infection that is associated with high mortality in immunocompromised individuals. While rhinocerebral and pulmonary forms are most common, primary gastrointestinal mucormycosis is very uncommon. The stomach is the most commonly affected organ followed by the colon and ileum in alimentary zygomycosis. We report a rare case of invasive gastric mucormycosis in a 50-year-old diabetic gentleman with a history of chronic alcoholism presenting with complaints of pain and distension of the abdomen for 6 days associated with fever, nausea, vomiting and anorexia. At presentation, he was hemodynamically unstable, febrile with uncontrolled blood sugar level and had negative HIV serology. There was generalized guarding, rigidity and distension of the abdomen and investigations confirmed perforative peritonitis. Upon exploration, there was solitary large 4 × 4 cm size perforated ulcer in the gastric body with greenish, greyish sloughed out mucosa within. Wedge resection of the ulcer with primary closure was performed. Histopathology revealed aseptate, broad, obtuse angled fungal hyphae, and invasive mucormycosis was confirmed by special stains like Periodic acid-Schiff (PAS) and Gomori's methenamine silver (GMS). Very few cases of invasive gastric mucormycosis associated with uncontrolled diabetes and alcoholism have been reported in the literature. Delayed presentation of the patient along with rapid progression to fungal septicaemia resulted in the case fatality despite early surgical intervention and critical care management.